Design, synthesis, and biological evaluation of 1,5-benzothiazepine-4-one derivatives targeting factor VIIa/tissue factor

被引：9

作者：

Ayral, Erwan ^{[2
]}

Gloanec, Philippe ^{[1
]}

Berge, Gilbert ^{[2
]}

de Nanteuil, Guillaume ^{[1
]}

Mennecier, Philippe ^{[3
]}

Rupin, Alain ^{[3
]}

Verbeuren, Tony J. ^{[3
]}

Fulcrand, Pierre ^{[2
]}

Martinez, Jean ^{[2
]}

Hernandez, Jean-Francois ^{[2
]}

机构：

[1] Inst Rech Servier, Div Med Chem D, F-92150 Suresnes, France

[2] Univ Montpellier 2, Univ Montpellier 1, CNRS, Inst Biomol Max Mousseron,UMR5247,Fac Pharm, F-34093 Montpellier 5, France

[3] Inst Rech Servier, Div Angiol, F-92150 Suresnes, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 05期

关键词：

Factor VIIa; Inhibitors; 1,5-Benzothiazepin-4-one; FACTOR-VIIA INHIBITORS; FACTOR XA; ANTICOAGULANT AGENTS; ORAL BIOAVAILABILITY; SELECTIVE INHIBITORS; POTENT; COMPLEX; OPTIMIZATION; DISCOVERY; THROMBIN;

D O I：

10.1016/j.bmcl.2009.01.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 1,5-benzothiazepine-4-one scaffold was earlier shown to provide efficient protease inhibitors. In this contribution, we describe its use in the design of factor VIIa/tissue factor inhibitors. A series containing a scaffold non-substituted on its aryl part led to compound 20 with an IC50 of 2.16 mu M. Following molecular modelling studies of this compound, a second series was prepared, which necessitated the synthesis of protected 7- or 8-substituted 1,5-benzothiazepine-4-one derivatives. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1386 / 1391

页数：6

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